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Activated PI 3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature
Author(s) -
Olbrich Peter,
Lorenz Myriam,
Cura Daball Paola,
Lucena José Manuel,
RensingEhl Anne,
Sanchez Berta,
Führer Marita,
CamachoLovillo Marisol,
Melon Marta,
Schwarz Klaus,
Neth Olaf,
Speckmann Carsten
Publication year - 2016
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12585
Subject(s) - medicine , apds , hematopoietic stem cell transplantation , transplantation , immunology , immunosuppression , disease , oncology , detector , electrical engineering , engineering , avalanche photodiode
Background Autosomal dominant gain‐of‐function mutations in PIK 3R1 encoding for the regulatory subunit (p85α, p55α, and p50α) of Class IA phosphoinositide 3‐kinase ( PI 3K) result in the activated PI 3Kδ syndrome ( APDS ) type 2 characterized by childhood‐onset combined immunodeficiency, lymphoproliferation, and immune dysregulation. To improve clinical awareness and understanding of these rare diseases, we reviewed all hitherto published cases with APDS type 1 and type 2 for their clinical and immunologic symptoms and added novel clinical, immunologic, and genetic findings of two patients with APDS type 2. Methods Clinical, immunologic, and genetic evaluation of two new patients with APDS 2 was performed followed by the systematic collection of all available previously published data of patients with APDS 1 and APDS 2. Results Patients with APDS type 1 (n = 49) and type 2 (n = 15) showed an indistinguishable immunologic phenotype. Overlapping clinical features shared by APDS type 1 and type 2 were observed, but our review also revealed previously unnoticed clinical differences such as remarkably high incidence of microcephaly, poor growth/short stature in patients with APDS 2. Clinical management and outcome were variable and included prophylactic antibiotics, immunosuppression, immunoglobulin substitution, and hematopoietic stem cell transplantation. Conclusions A disease‐specific registry collecting prospective and long‐term follow‐up data of patients with APDS , as currently set up by the European Society for Immunodeficiencies, are needed to better understand the natural history and to optimize treatment concepts and thereby improving the outcome of this heterogenous patient group.